On Effect Size Measures for Nested Measurement Models.

A class of effect size indices are discussed that evaluate the degree to which two nested confirmatory factor analysis models differ from each other in terms of fit to a set of observed variables. These descriptive effect measures can be used to quantify the impact of parameter restrictions imposed in an initially considered model and are free from an explicit relationship to sample size. The described indices represent the extent to which respective linear combinations of the proportions of explained variance in the manifest variables are changed as a result of introducing the constraints. The indices reflect corresponding aspects of the impact of the restrictions and are independent of their statistical significance or lack thereof. The discussed effect size measures are readily point and interval estimated, using popular software, and their application is illustrated with numerical examples.

Pleiotropic MLLT10 variation confers risk of meningioma and estrogen-mediated cancers.

Background: Risk of tumors of the breast, ovary, and meninges has been associated with hormonal factors and with one another. Genome-wide association studies (GWAS) identified a meningioma risk locus on 10p12 near previous GWAS hits for breast and ovarian cancers, raising the possibility of genetic pleiotropy. Methods: We performed imputation-based fine-mapping in three case-control datasets of meningioma (927 cases, 790 controls), female breast cancer (28 108 cases, 22 209 controls), and ovarian cancer (25 509 cases, 40 941 controls). Analyses were stratified by sex (meningioma), estrogen receptor (ER) status (breast), and histotype (ovarian), then combined using subset-based meta-analysis in ASSET. Lead variants were assessed for association with additional traits in UK Biobank to identify potential effect-mediators. Results: Two-sided subset-based meta-analysis identified rs7084454, an expression quantitative trait locus (eQTL) near the MLLT10 promoter, as lead variant (5.7 × 10-14). The minor allele was associated with increased risk of meningioma in females (odds ratio (OR) = 1.42, 95% Confidence Interval (95%CI):1.20-1.69), but not males (OR = 1.19, 95%CI: 0.91-1.57). It was positively associated with ovarian (OR = 1.09, 95%CI:1.06-1.12) and ER+ breast (OR = 1.05, 95%CI: 1.02-1.08) cancers, and negatively associated with ER- breast cancer (OR = 0.91, 95%CI: 0.86-0.96). It was also associated with several adiposity traits (P < 5.0 × 10-8), but adjusting for body mass index did not attenuate its association with meningioma. MLLT10 and ESR1 expression were positively correlated in normal meninges (P = .058) and meningioma tumors (P = .0065). Conclusions: We identify a MLLT10 eQTL positively associated with risk of female meningioma, ER+ breast cancer, ovarian cancer, and obesity, and implicate a potential estrogenic mechanism underlying this pleiotropy.

Model Selection and Average Proportion Explained Variance in Exploratory Factor Analysis.

A procedure for evaluating the average R-squared index for a given set of observed variables in an exploratory factor analysis model is discussed. The method can be used as an effective aid in the process of model choice with respect to the number of factors underlying the interrelationships among studied measures. The approach is developed within the framework of exploratory structural equation modeling and is readily applicable with popular statistical software. The outlined procedure is illustrated using a numerical example.

Translation and Cross-Cultural Adaptation of the Family Accommodation Scale for Obsessive-Compulsive Disorder Into Chinese.

Family accommodation is a phenomenon that has been associated with worse treatment outcome of patients with obsessive-compulsive disorder (OCD) and greater severity of symptoms and levels of functional impairment. Yet, there are no Chinese scales to assess family accommodation in OCD among family members. The present study aimed to illustrate the steps of translation and cross-cultural adaptation of the Chinese versions of the Family Accommodation Scale (FAS). After obtaining authorization of the developers, the Chinese versions of the FAS were translated and adapted from the English versions based on a standard protocol, following six steps: forward translation, pilot administration, language adjustment and cultural adaptation, back-translation, review and minor edit, and final approval of the developer. Thirty-five pairs of patients and corresponding relatives with different education levels were administered the FAS in the pretest stage. This study found that the semantic, idiomatic, and conceptual equivalence were obtained between the Chinese versions and original English scales, and the Chinese versions of FAS were well translated and culturally adapted. We also found that the Chinese versions of the FAS can be easily understood by people of different socioeconomic statuses.

Social media partnerships with patient organizations for neuro-oncology patient recruitment.

BACKGROUND: In neuro-oncology, traditional methods of enrolling the large numbers of participants required for studies of disease etiology and treatment response are costly, labor intensive, and may not include patients in regions without tumor registries. METHODS: In the Yale Acoustic Neuroma (AN) Study and International Low-Grade Glioma (LGG) Registry, we partnered with several brain tumor patient organizations to develop social media enrollment campaigns and use web-based data collection resources at the Yale University School of Public Health to test alternative methods to enroll neuro-oncology patients for epidemiologic study. RESULTS: In the AN study, we enrolled 1024 patients over 2 years. Of these, 865 patients completed the online questionnaire, 697 returned written consent, 583 sent a pathology report, and 569 returned a saliva specimen. The completed 569 participants did not differ by age or treatment from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data but were more likely to be female (67% vs 52%) and white (94.8% vs 84%). Patients learned of the study through the Acoustic Neuroma Association (ANA) website (61.3%), ANA support group members (18%), and social media (primarily Facebook). Costs per patient enrolled were approximately 10% to 20% that of traditional registry-based enrollment methods. Results for the LGG study were similar. CONCLUSIONS: Although additional effort will be required to ensure a diverse participant population, partnership with established patient organizations along with use of web-based technology and social media allowed for the successful enrollment of neuro-oncology patients at a fraction of the cost relative to traditional methods.

Quality and Publication of Emergency Medicine Trials Registered in ClinicalTrials.gov

INTRODUCTION: Promoting emergency medicine (EM) clinical trials research remains a priority. To characterize the status of clinical EM research, this study assessed trial quality, funding source, and publication of EM clinical trials and compared EM and non-EM trials on these key metrics. We also examined the volume of EM trials and their subspecialty areas. METHODS: We abstracted data from ClinicalTrials.gov (February 2000 - September 2013) and used individual study National Clinical Trial numbers to identify published trials (January 2007 - September 2016). We used descriptive statistics and chi-square tests to examine study characteristics by EM and non-EM status, and Kaplan-Meier curves and log-rank tests to compare time to publication of completed EM and non-EM studies. RESULTS: We found 638 interventional EM trials and 59,512 non-EM interventional trials conducted in the United States between February 2000 and September 2013, registered on ClinicalTrials.gov. EM studies were significantly less likely than non-EM studies to be National Institutes of Health-funded or to evaluate a drug or biologic. However, EM studies had significantly larger sample sizes, and were significantly more likely to use randomization and blinding. Overall, 34.3% of EM and 26.0% of non-EM studies were published in peer-reviewed journals. By subspecialty, more EM trials concerned medical/surgical and psychiatric/neurological conditions than trauma. CONCLUSION: Although EM studies were less likely to have received federal or industry funding, and the EM portfolio consisted of only 638 trials over the 14-year study period, the quality of EM trials surpassed that of non-EM trials, based on indices such as randomization and blinding. This novel finding bodes well for the future of clinical EM research, as does the higher proportion of published EM than non-EM trials. Our study also revealed that trauma studies were under-represented among EM studies. Periodic assessment of EM trials with the metrics used here could provide an informative and valuable longitudinal view of progress in clinical EM research.

Mendelian randomization provides support for obesity as a risk factor for meningioma.

Little is known about the causes of meningioma. Obesity and obesity-related traits have been reported in several epidemiological observational studies to be risk factors for meningioma. We performed an analysis of genetic variants associated with obesity-related traits to assess the relationship with meningioma risk using Mendelian randomization (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. We considered 11 obesity-related traits, identified genetic instruments for these factors, and assessed their association with meningioma risk using data from a genome-wide association study comprising 1,606 meningioma patients and 9,823 controls. To evaluate the causal relationship between the obesity-related traits and meningioma risk, we consider the estimated odds ratio (OR) of meningioma for each genetic instrument. We identified positive associations between body mass index (odds ratio [ORSD] = 1.27, 95% confidence interval [CI] = 1.03-1.56, P = 0.028) and body fat percentage (ORSD = 1.28, 95% CI = 1.01-1.63, P = 0.042) with meningioma risk, albeit non-significant after correction for multiple testing. Associations for basal metabolic rate, diastolic blood pressure, fasting glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, systolic blood pressure, total cholesterol, triglycerides and waist circumference with risk of meningioma were non-significant. Our analysis provides additional support for obesity being associated with an increased risk of meningioma.

Validation of the International Guide for Monitoring Child Development demonstrates good sensitivity and specificity in four diverse countries.

AIM: It is of critical importance to have internationally constructed tools to address early childhood development. The aim of this second phase of a two-phase study was to examine the sensitivity and specificity of the Guide for Monitoring Child Development (GMCD) in identifying developmental delay in four diverse countries. METHODS: The first phase of this 2011-2015 back-to-back study included 4949 children up to 42 months of age from primary healthcare centres in Argentina, India, South Africa and Turkey. Distribution curves were generated to show the ages when the children attained GMCD milestones and those that could be used across sexes and countries were placed in age ranges corresponding to the 85th and 97th percentile point estimates. Phase two examined a separately recruited sample of children in those countries to determine sensitivity and specificity of the GMCD. RESULTS: The validation phase of the 85 milestones in the GMCD identified delayed development in 30% of the 1731 children in the four countries. The sensitivity and specificity ranged from 0.71-0.94 and 0.69-0.82, respectively, for the total sample and the different age groups. CONCLUSION: The GMCD standardised in four diverse countries has appropriate accuracy for identification of children with developmental delay.

Prostate cancer aggressiveness and age: Impact of p53, BCL-2 and microvessel density.

Older men are more likely to have advanced prostate cancer at time of their diagnosis, but whether prostate tumors are inherently (biologically) more aggressive with advancing age is uncertain. To address this gap in knowledge, we analyzed data from veterans (n=971) diagnosed with prostate cancer during 1991-1995. Factors included age, detection of prostate cancer by screening, prostate-specific antigen (PSA) level, anatomic stage, and Gleason score. Information on molecular markers obtained from immunohistochemical staining of prostate tissue, included B cell lymphoma-2 (bcl-2), p53, and microvessel density (MVD), each having a previously documented association with disease progression and increased risk of prostate cancer death. We first examined the bivariate association of demographic, clinical, and molecular factors with age, and found evidence that race, screening status, Gleason score, PSA, bcl-2, p53, and MVD varied across categories of age in this study population. After further characterizing the association between age and Gleason score, we used logistic regression to examine the association between age and molecular markers-accounting for race, screening status, PSA, and Gleason score. Comparing men older than 80 years to those younger than 70 years, adjusted ORs and 95% CIs were 1.89 (0.73 to 4.92), 1.91 (1.05 to 3.46), and 2.00 (1.06 to 3.78), for positive bcl-2, p53, and MVD markers, respectively; no statistically significant associations were found for men 70-79 years old, compared with men younger than 70 years. These novel findings suggest that very elderly men often present with biologically aggressive prostate cancer; the results also have potential implications for therapeutic decision-making.

Genome-wide association analysis identifies a meningioma risk locus at 11p15.5.

Background: Meningiomas are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31. Methods: To identify a susceptibility locus for meningioma, we conducted a meta-analysis of 2 GWAS, imputed using a merged reference panel from the 1000 Genomes Project and UK10K data, with validation in 2 independent sample series totaling 2138 cases and 12081 controls. Results: We identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges. Conclusions: This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.

Similarities and differences in child development from birth to age 3 years by sex and across four countries: a cross-sectional, observational study.

BACKGROUND: Knowledge about typical development is of fundamental importance for understanding and promoting child health and development. We aimed to ascertain when healthy children in four culturally and linguistically different countries attain developmental milestones and to identify similarities and differences across sexes and countries. METHODS: In this cross-sectional, observational study, we recruited children aged 0-42 months and their caregivers between March 3, 2011, and May 18, 2015, at 22 health clinics in Argentina, India, South Africa, and Turkey. We obtained a healthy subsample, which excluded children with a low birthweight, perinatal complications, chronic illness, undernutrition, or anaemia, and children with missing health data. Using the Guide for Monitoring Child Development, caregivers described their child's development in seven domains: expressive and receptive language, gross and fine motor, play, relating, and self-help. Clinicians examining the children also completed a checklist about the child's health status. We used logit and probit regression models based on the lowest deviance information criterion to generate Bayesian point estimates and 95% credible intervals for the 50th percentile ages of attainment of 106 milestones. We assessed the significance of differences between sexes and countries using predefined criteria and regions of practical equivalence. FINDINGS: Of 10 246 children recruited, 4949 children (48·3%) were included in the healthy subsample. For the 106 milestones assessed, the median age of attainment was equivalent for 102 (96%) milestones across sexes and 81 (76%) milestones across the four countries. Across countries, median ages of attainment were equivalent for all play milestones, 20 (77%) of 26 expressive language milestones, ten (67%) of 15 receptive language milestones, nine (82%) of 11 fine motor milestones, 14 (88%) of 16 gross motor milestones, and eight (73%) of 11 relating milestones. However, across the four countries the median age of attainment was equivalent for only two (22%) of nine milestones in the self-help domain. INTERPRETATION: The ages of attainment of developmental milestones in healthy children, and the similarities and differences across sexes and country samples might aid the development of international tools to guide policy, service delivery, and intervention research, particularly in low-income and middle-income countries. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Psychometric properties of the Family Accommodation Scale for Obsessive-Compulsive Disorder-Patient Version.

In obsessive-compulsive disorder (OCD), family accommodation is a frequently occurring phenomenon that has been linked to attenuated treatment response, increased obsessive-compulsive symptom severity, and lower levels of functioning. No patient-report version of family accommodation exists, with available measures relying on relatives as informants. However, adult patients with OCD often present to clinical services alone, frequently making it impractical to obtain information from these informants. Consequently, a standardized patient-reported measure of family accommodation proves salient in clinical practice. The present study examined the psychometric properties of the Family Accommodation Scale for Obsessive-Compulsive Disorder-Patient Version (FAS-PV). Sixty-one adults with OCD were administered clinician-rated measures of OCD symptom severity and self-report questionnaires examining functional impairment, family functioning, and emotional/behavioral difficulties. Fifty-four relatives completed self-report measures assessing family accommodation and family functioning. The majority of the adult OCD participants (89%) endorsed at least 1 type of accommodating behavior in the previous week. The FAS-PV total score demonstrated good internal consistency and test-retest reliability. Convergent validity was evidenced by strong associations with scores on another measure of family accommodation, OCD symptom severity, OCD-related family functioning, anxiety, and functional impairment. Divergent validity was supported through nonsignificant correlations with depressive symptoms and impulsivity. The FAS-PV did not significantly differ from the relative-reported measure of family accommodation in terms of the internal consistency or mean of the total scores. Ultimately, the FAS-PV scores demonstrated sound psychometric properties and validity in assessing family accommodation from the patient's perspective, encouraging its use in research and clinical practice.

Endogenous and exogenous hormone exposure and the risk of meningioma in men.

OBJECT: Meningioma is a disease with considerable morbidity and is more commonly diagnosed in females than in males. Hormonally related risk factors have long been postulated to be associated with meningioma risk, but no examination of these factors has been undertaken in males. METHODS: Subjects were male patients with intracranial meningioma (n = 456), ranging in age from 20 to 79 years, who were diagnosed among residents of the states of Connecticut, Massachusetts, and North Carolina, the San Francisco Bay Area, and 8 counties in Texas and matched controls (n = 452). Multivariate logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between hormonal factors and meningioma risk in men. RESULTS: Use of soy and tofu products was inversely associated with meningioma risk (OR 0.50 [95% CI 0.37-0.68]). Increased body mass index (BMI) appears to be associated with an approximately 2-fold increased risk of developing meningioma in men. No other single hormone-related exposure was found to be associated with meningioma risk, although the prevalence of exposure to factors such as orchiectomy and vasectomy was very low. CONCLUSIONS: Estrogen-like exogenous exposures, such as soy and tofu, may be associated with reduced risk of meningioma in men. Endogenous estrogen-associated factors such as high BMI may increase risk. Examination of other exposures related to these factors may lead to better understanding of mechanisms and potentially to intervention.

Development and preliminary psychometric evaluation of a self-rated version of the Family Accommodation Scale for Obsessive-Compulsive Disorder.

Family accommodation (FA) in obsessive-compulsive disorder (OCD) refers to family members' or significant others' participation in or facilitation of patients' rituals and/or avoidance. With recent studies pointing to FA as a predictor of poorer treatment outcome, there is heightened interest in developing family-based interventions for OCD aimed at reducing FA. The interviewer-rated Family Accommodation Scale for OCD (FAS-IR) is the gold standard for assessing the types and severity of FA in OCD families. However, the cost of training interviewers and the time required for administration may limit its use in some settings. A valid self-rated version could be administered for research and clinical purposes with minimal burden and has the potential to be more widely used. The present study reports on the development and initial psychometric testing of the Family Accommodation Scale for OCD-Self Rated Version (FAS-SR). The FAS-SR was compared to the FAS-IR in a sample of 41 relatives of individuals with primary OCD, demonstrating excellent internal consistency, strong agreement with the FAS-IR, and expected convergence with criterion measures. Though further study using the self-rated version is needed, these findings suggest that the FAS-SR is a valid measure of FA and a time-saving, less costly alternative to the FAS-IR.

Family accommodation in pediatric anxiety disorders.

BACKGROUND: Family accommodation has been studied in obsessive compulsive disorder using the Family Accommodation Scale (FAS) and predicts greater symptom severity, more impairment, and poorer treatment outcomes. However, family accommodation has yet to be systematically studied among families of children with other anxiety disorders. We developed the Family Accommodation Scale-Anxiety (FASA) that includes modified questions from the FAS to study accommodation across childhood anxiety disorders. The objectives of this study were to report on the first study of family accommodation across childhood anxiety disorders and to test the utility of the FASA for assessing the phenomenon. METHODS: Participants were parents (n = 75) of anxious children from two anxiety disorder specialty clinics (n = 50) and a general outpatient clinic (n = 25). Measures included FASA, structured diagnostic interviews, and measures of anxiety and depression. RESULTS: Accommodation was highly prevalent across all anxiety disorders and particularly associated with separation anxiety. Most parents reported participation in symptoms and modification of family routines as well as distress resulting from accommodation and undesirable consequences of not accommodating. The FASA displayed good internal consistency and convergent and divergent validity. Accommodation correlated significantly with anxious but not depressive symptoms, when controlling for the association between anxiety and depression. Factor analysis of the FASA pointed to a two-factor solution; one relating to modifications, the other to participation in symptoms. CONCLUSIONS: Accommodation is common across childhood anxiety disorders and associated with severity of anxiety symptoms. The FASA shows promise as a means of assessing family accommodation in childhood anxiety disorders.

Exogenous hormone use, reproductive factors, and risk of intracranial meningioma in females.

OBJECT: The 2-fold higher incidence of meningioma in women compared with men has long suggested a role for hormonally mediated risk factors, but specific mechanisms remain elusive. METHODS: The study included data obtained in 1127 women 29-79 years of age with intracranial meningioma diagnosed among residents of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area, and 8 Texas counties between May 1, 2006, and October 6, 2011, and data obtained in 1092 control individuals who were frequency matched for age group and geography with meningioma patients. RESULTS: No association was observed for age at menarche, age at menopause, or parity and meningioma risk. Women who reported breastfeeding for at least 6 months were at reduced risk of meningioma (OR 0.78, 95% CI 0.63-0.96). A significant positive association existed between meningioma risk and increased body mass index (p < 0.01) while a significant negative association existed between meningioma risk and current smoking (p < 0.01). Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1-2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74-1.67). There was no association between use of fertility medications and meningioma risk. CONCLUSIONS: The authors' study confirms associations for body mass index, breastfeeding, and cigarette smoking but provides little evidence for associations of reproductive and menstrual factors with meningioma risk. The relationship between current use of exogenous hormones and meningioma remains unclear, limited by the small numbers of patients currently on oral hormone medications and a lack of hormone receptor data for meningioma tumors.

Assessment of autoantibodies to meningioma in a population-based study.

Meningioma is an intracranial tumor with few confirmed risk factors. Recent research points to an impact on meningioma risk from factors related to immune function and development, such as allergy, immunoglobulin E, and Varicella infection status. To further explore an association with immune function, the authors assessed individual seroreactivity to meningioma tumor-associated antigens among participants enrolled in a multicenter, population-based US case-control study of meningioma (2006-2009). Serum samples from cases (n = 349) and controls (n = 348) were screened for autoantibody reactivity to 3 proteins identified in previous studies: enolase 1 (ENO1), NK-tumor recognition protein (NKTR), and nuclear mitotic apparatus protein 1 (NUMA1). Case-control differences were not strong overall (adjusted odds ratio (OR)(ENO1 (continuous)) = 1.1, 95% confidence interval (CI): 0.6, 1.9 (P(trend) = 0.3); adjusted OR(NKTR (continuous)) = 1.3, 95% CI: 0.7, 2.4 (P(trend) = 0.02); and adjusted OR(NUMA1 (continuous)) = 1.1, 95% CI: 0.7, 1.8 (P(trend) = 0.06)); however, antibodies to NKTR and NUMA1 were detected at higher levels in cases than in controls, particularly among men (for men, adjusted OR(ENO1 (continuous)) = 1.6, 95% CI: 0.5, 4.7 (P(trend) = 0.24); adjusted OR(NKTR (continuous)) = 4.3, 95% CI: 1.2, 15 (P(trend) = 0.009); and adjusted OR(NUMA1 (continuous)) = 3.6, 95% CI: 1.1, 11 (P(trend) = 0.006)). These results indicate that men with meningioma commonly react with a serologic antimeningioma response; if supported by further research, this finding suggests a distinctive etiology for meningioma in men.

Dental x-rays and risk of meningioma.

BACKGROUND: Ionizing radiation is a consistently identified and potentially modifiable risk factor for meningioma, which is the most frequently reported primary brain tumor in the United States. The objective of this study was to examine the association between dental x-rays-the most common artificial source of ionizing radiation-and the risk of intracranial meningioma. METHODS: This population-based case-control study included 1433 patients who had intracranial meningioma diagnosed at ages 20 to 79 years and were residents of the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area, and 8 counties in Houston, Texas between May 1, 2006 and April 28, 2011 (cases). A control group of 1350 individuals was frequency matched on age, sex, and geography (controls). The main outcome measure for the study was the association between a diagnosis of intracranial meningioma and self-reported bitewing, full-mouth, and panorex dental x-rays. RESULTS: Over a lifetime, cases were more than twice as likely as controls (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.4-2.9) to report having ever had a bitewing examination. Regardless of the age at which the films were obtained, individuals who reported receiving bitewing films on a yearly basis or with greater frequency had an elevated risk for ages <10 years (OR, 1.4; 95% CI, 1.0-1.8), ages 10 to 19 years (OR, 1.6; 95% CI, 1.2-2.0), ages 20 to 49 years (OR, 1.9; 95% CI, 1.4-2.6), and ages ≥40 years (OR, 1.5; 95% CI, 1.1-2.0). An increased risk of meningioma also was associated with panorex films taken at a young age or on a yearly basis or with greater frequency, and individuals who reported receiving such films at ages <10 years had a 4.9 times increased risk (95% CI, 1.8-13.2) of meningioma. No association was appreciated for tumor location above or below the tentorium. CONCLUSIONS: Exposure to some dental x-rays performed in the past, when radiation exposure was greater than in the current era, appears to be associated with an increased risk of intracranial meningioma. As with all sources of artificial ionizing radiation, considered use of this modifiable risk factor may be of benefit to patients.

Cigarette smoking and risk of meningioma: the effect of gender.

BACKGROUND: A number of studies have reported on the association between smoking and meningioma risk, with inconsistent findings. We examined the effect of gender on the association between cigarette smoking and risk of intracranial meningioma in a large population-based, case-control study. METHODS: The data include 1,433 intracranial meningioma cases aged 29 to 79 years diagnosed among residents of the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area and eight Texas counties between May 1, 2006 and April 28, 2011 as well as 1,349 controls that were frequency matched on age, sex, and geography. The data are analyzed separately and in a meta-analysis with six previously reported studies. RESULTS: Female cases who reported having ever smoked were at significantly decreased risk of intracranial meningioma (OR, 0.8; 95% CI, 0.7-0.9) in contrast to male cases who were at increased risk (OR, 1.3; 95% CI, 1.0-1.7). Similar findings were noted for current and past smokers. Smoking-induced risk for females did not vary by menopausal status. For males, increased duration of use (P = 0.04) as well as increasing number of pack-years (P = 0.02) was associated with elevated risk. A meta-analysis including 2,614 cases and 1,179,686 controls resulted in an OR for ever smoking of 0.82 (95% CI, 0.68-0.98) for women and 1.39 (95% CI, 1.08-1.79) for men. CONCLUSION: The association of cigarette smoking and meningioma case status varies significantly by gender with women at reduced risk and men at greater risk. IMPACT: Whether the observed differences are associated with a hormonal etiology will require additional investigation.

Postmenopausal hormone therapy and ductal carcinoma in situ: a population-based case-control study.

BACKGROUND AND AIM: The relationship between hormone therapy (HT) and invasive breast cancer has been extensively investigated, but the relationship between HT and in situ breast cancer has received relatively little attention. We examined the relationship between HT and ductal carcinoma in situ (DCIS) among postmenopausal women who participated in a population-based case-control study in Connecticut, USA. METHODS: This analysis included 1179 post-menopausal women (603 controls and 576 cases), who comprised a subset of a population-based case-control study that included all incident cases of breast carcinoma in situ (BCIS) in Connecticut and frequency-matched controls by 5-year age intervals. RESULTS: We found no association between DCIS and ever use of any HT (adjusted odds ratio (OR)=0.85, 95% confidence interval (CI): 0.65-1.11); of estrogen alone (adjusted OR=0.93; 95% CI: 0.68-1.29) or of estrogen and progesterone (adjusted OR=0.75; 95% CI: 0.52-1.08). There was also no association between DCIS and current use of these hormones. In addition, estimated risk of DCIS did not increase with duration of use of these preparations. CONCLUSIONS: These results add to a small literature that remains inconclusive. To determine whether HT poses risk of in situ breast cancer, larger studies with greater power and precise control of important covariates (e.g., mammography screening) are needed, as are meta-analyses of available data.